A mechanism for circadian control of pacemaker neuron excitability

Marc Ruben, Mark D. Drapeau, Dogukan Mizrak, Justin Blau

Research output: Contribution to journalArticlepeer-review


Although the intracellular molecular clocks that regulate circadian (∼24 h) behavioral rhythms are well understood, it remains unclear how molecular clock information is transduced into rhythmic neuronal activity that in turn drives behavioral rhythms. To identify potential clock outputs, the authors generated expression profiles from a homogeneous population of purified pacemaker neurons (LNvs) from wild-type and clock mutant Drosophila. They identified a group of genes with enriched expression in LNvs and a second group of genes rhythmically expressed in LNvs in a clock-dependent manner. Only 10 genes fell into both groups: 4 core clock genes, including period (per) and timeless (tim), and 6 genes previously unstudied in circadian rhythms. The authors focused on one of these 6 genes, Ir, which encodes an inward rectifier K+ channel likely to regulate resting membrane potential, whose expression peaks around dusk. Reducing Ir expression in LN vs increased larval light avoidance and lengthened the period of adult locomotor rhythms, consistent with increased LNv excitability. In contrast, increased Ir expression made many adult flies arrhythmic and dampened PER protein oscillations. The authors propose that rhythmic Ir expression contributes to daily rhythms in LNv neuronal activity, which in turn feed back to regulate molecular clock oscillations.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalJournal of Biological Rhythms
Issue number5
StatePublished - Oct 2012


  • Drosophila
  • circadian rhythm
  • circadian transcription
  • expression profiling
  • inward rectifier channel
  • pacemaker neuron

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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